There are very limited options currently available for the treatment of HPV(-) head and neck squamous cell cancer (HNSCC), the sixth leading cause of cancer in the United States and worldwide. HNSCC, like most forms of cancer, is dependent on angiogenesis, the growth of blood vessels. We have developed a mimetic multimodal peptide that inhibits growth of tumor angiogenesis and directly inhibits tumor cell adhesion and migration. Tumors treated with this multimodal peptide are less likely to develop resistance to therapy because it inhibits signals from a broad range of tumor-secreted factors. In this project we will create a novel targeted nanoparticle delivery vehicle for this peptide. The nanoparticle-encapsulated peptide will be administered systemically and will accumulate in the tumor and its vasculature in order to enhance both efficacy and safety. Successful completion of the project will result in the creation of a powerful, new therapeutic for the treatment of HNSCC and also help a startup biotechnology company reach a critical milestone.